Reaktion #44858

Reaktionsgleichung

tert-butyl 4-{[4-(aminomethyl)piperidin-1-yl]methyl}tetrahydro-2H-pyran-4-carboxylate

1-isopropyl-1,3-dihydro-2H-benzimidazol-2-one

Et3N

NaHCO3

→

title compound

Ausbeute 100.0%

tert-butyl 4-{[4-({[(3-isopropyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)carbonyl]amino}methyl)piperidin-1-yl]methyl}tetrahydro-2H-pyran-4-carboxylate

Ausbeute 100.0%

Lösungsmittel

CH2Cl2

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGthe resulting mixture was stirred at room temperature for 24 h
2. 2
   Extraktionextracted with CH2Cl2 (300 mL) for three times
3. 3
   ExtraktionThe combined extract
4. 4
   Trocknenwas dried over Na2SO4
5. 5
   Einengenconcentrated
6. 6
   SonstigeThe residue was chromatographed on a column of NH-silica gel eluting with hexane/ethyl acetate (1:1)

Vorschrift

A mixture of p-nitrophenylchloroformate (4.14 g, 0.0205 mol), 1-isopropyl-1,3-dihydro-2H-benzimidazol-2-one (3.62 g, 0.0205 mol, J. Med. Chem. 1999, 42, 2870-2880) and Et3N (7.81 mL, 0.0560 mol) in CH2Cl2 (100 mL) was stirred at room temperature for 4 h. Then, tert-butyl 4-{[4-(aminomethyl)piperidin-1-yl]methyl}tetrahydro-2H-pyran-4-carboxylate (5.72 g, 0.0187 mol, step 5) was added, and the resulting mixture was stirred at room temperature for 24 h. The reaction mixture was diluted with sat. NaHCO3 aq. (300 mL), extracted with CH2Cl2 (300 mL) for three times. The combined extract was dried over Na2SO4 and concentrated. The residue was chromatographed on a column of NH-silica gel eluting with hexane/ethyl acetate (1:1) to give 9.83 g (100%) of the title compound as a yellow syrup.

Quelle